The present invention relates to a process for producing mannitol-rich solutions of sorbitol and mannitol. More particularly, this invention relates to a process for producing a mannitol-rich solution of sorbitol and mannitol from glucose.
It is well known that a mixture of sorbitol and mannitol in aqueous solution can be produced by catalytic hydrogenation of invert sugar, which is an approximately equimolar mixture of glucose and fructose. Invert sugar, in turn, is commonly obtained by inversion of sucrose (ordinary sugar). The yield of mannitol is ordinarily about 24-26 percent by weight, based on total dry solids, when hydrogenation is carried out under neutral or mildly acidic conditions, such as those disclosed in U.S. Pat. No. 2,759,024 to Kasehagen et al. (The theoretical yield of mannitol is about 25 percent by weight of total dry solids, assuming that no isomerization takes place). This yield can be increased by carrying out at least part of the hydrogenation under alkaline conditions, as described in U.S. Pat. Nos. 3,329,729 to Brandner et al., and 3,763,246 to deBerardinis, or by appropriate choice of catalyst, as described in U.S. Pat No. 3,705,199 to deBerardinis, or both. The reaction products obtained according to the processes of these patents contain about 30-36 percent mannitol, about 27-31 percent mannitol, and about 28- 29 percent mannitol, all on the dry basis, respectively. In each case the balance of the reaction product is mostly sorbitol.
Enhanced yields of mannitol under alkaline hydrogenation conditions are due to isomerization of part of the glucose present to fructose and mannose. The proportions of glucose, fructose, and mannose in the reaction mixture will vary depending on the alkaline material and the conditions used, and significant quantities of mannose are not ordinarily obtained. Such isomerization is well known in the art, and is discussed, for example, in U.S. Pat. Nos. 3,329,729 and 3,763,246 cited supra, and in Pigman, "The Carbohydrates: Chemistry, Biochemistry, and Physiology," Academic Press, New York, 1957, pages 60-69.
Mannitol may be recovered from aqueous solutions containing both sorbitol and mannitol by fractional crystallization, as described for example in U.S. Pat. No. 3,632,656.
Although enhanced yields of mannitol are obtained under alkaline hydrogenation conditions, the proportion of impurities formed under alkaline hydrogenation conditions is also higher than the proportion formed under neutral or acid hydrogenation conditions. Impurities obtained under alkaline hydrogenation conditions include ethylene glycol, propylene glycol, and glycerine.
Hydrogenation of invert sugar is an attractive commercial route to the production of mannitol when the price of sucrose (ordinary sugar) is low. However, sharp rises and fluctuations in the price of sucrose in recent years have indicated a need for alternate routes.
High costs of mannose and fructose in substantially pure form preclude the economic use of these sugars as starting materials, even though mannose yields essentially pure mannitol and fructose yields a 50:50 mixture of sorbitol and mannitol on catalytic hydrogenation. There is a need for a new process for preparing mannitol which uses an inexpensive starting material and which gives a higher yield of mannitol than present processes.
A process for obtaining sorbitol-mannitol solutions from glucose by first catalytically epimerizing glucose in an acidic usually solution to obtain an epimerizate of glucose and mannose, and then catalytically hydrogenating this epimerizate in an acidic aqueous solution to obtain an aqueous solution of sorbitol and mannitol, is described in my copending U.S. patent application, Ser. No. 578,548, filed May 19, 1975, now U.S. Pat. No. 4,029,878, issued June 14, 1977. Epimerization according to that process is carried out at elevated temperature in an acidic aqueous solution containing at least 50% solids and preferably about 67-70% solids, using a hexavalent molybdenum catalyst such as molybdic acid or an anion exchange resin in the molybdate form. Hydrogenation catalysts and conditions for hydrogenating the glucose-mannose epimerizate to a mixture of sorbitol and mannitol in that process are conventional. Ordinarily the epimerizate will contain about 30% (e.g., about 27-33%) of mannose on the dry basis, and the mol percentage of mannitol in the final product is also usualy about 30%; that is, the mol percentage of mannitol in the final product does not differ significantly from the mol percentage of mannose in the epimerizate.
Epimerization of glucose in aqueous solution into a mixture of glucose and mannose is also described by Bilik in Chem. Zvesti, 26, 183-186 (1972). In Bilik, a 17% (by weight) glucose solution containing 1% by weight of molybdic acids based on glucose, is used, and 25% of the glucose is epimerized to mannose.
The mannose yield obtained in my copending application is significantly higher than that obtained by Bilik. Also, the mannitol yield is significantly higher than those obtained by catalytic hydrogenation of invert sugar under acid or neutral conditions, which as stated above ordinarily yields about 25% mannitol, remainder sorbitol on the dry basis.
Enzymatic isomerization of glucose in aqueous solution to fructose has gained considerable attention in recent years as a means for producing a substitute for sucrose, and there is a considerable volume of patents and other published literature on this subject. Microorganisms of various genera are known to produce glucose isomerase, which is an enzyme capable of isomerizing glucose into fructose. The production and use of glucose isomerase derived from a Pseudomonas microorganism is described in U.S. Pat. No. 2,950,228. An article by Takasaki in "Fermentation Advances," D. Perlman, ed., Academic Press, 1969, pages 561-589, describes the use of glucose isomerase derived from Streptomyces microorganisms, either as a cell-free extract or in the form of heat treated whole cells of Streptomyces microorganisms, for isomerization of glucose to fructose. The enzyme also acts on xylose but not on mannose, arabinose, or ribose, according to Takasaki. The use of Arthrobacter-derived glucose isomerase for the isomerization of glucose to fructose is disclosed in U.S. Pat. Nos. 3,645,848; 3,821,086; 3,989,596; 3,989,597; Re. 29,130; and Re. 29,136. All of these patents except U.S. Pat. No. 3,645,848 disclose the use of flocculated whole Arthrobacter cells containing glucose isomerase. N. Tsumura et al., Agr. Biol. Chem. 25, 1961, pp. 616-619, describe the use of glucose isomerase derived from Aerobacter organisms, while K. Yamanaka, Agr. Biol. Chem. 27, 1963, pp. 265-270, describes the use of glucose isomerase obtained from Lactobacillus organisms. Other glucose isomerase-producing microorganisms are also known. Syrups containing about 40-45 percent by weight of fructose on the dry basis are obtainable by enzymatic isomerization. These syrups are used as sweeteners in various food products.
In carrying out an enzyme-catalyzed isomerization of glucose to fructose, the enzyme may be used in the form of a cell-free extract which is dissolved in the glucose solution, or in an immobilized form in or on a water-insoluble matrix. The matrix may comprise either living or inactivated whole microorganism cells, or may be any other suitable water-insoluble solid support. Takasaki, "Fermentation Advances" cited supra, illustrates both cell-free extracts and glucose isomerase immobilized in whole Streptomyces cells. U.S. Pat. Nos. 3,645,848 and 3,821,086 describe whole Arthrobacter cells containing glucose isomerase. Supports or carriers other than microorganism cells are also known; for example, U.S. Pat. Nos. 3,868,304 and 3,992,329 describe glucose isomerase immobilized on porous inorganic supports. The use of immobilized glucose isomerase is preferred because this permits both continuous column isomerization and repeated use of the enzyme. In contrast, glucose in the form of a cell-free extract can be used only in a batch type reaction and can be used only once, since it is impractical to recover the enzyme.